About epidemic keratoconjunctivitis (EKC) – a serious disease without effective treatment
Sometimes the term “pinkeye” is used which is a broader term for conjunctivitis caused by both bacteria and virus. Viral conjunctivitis is the more common cause and the majority of viral conjunctivitis are caused by adenovirus. Signs and symptoms of acute bacterial and acute viral conjunctivitis are essentially similar. For bacterial conjunctivitis there are topical antibiotics available but there is no treatment for viral conjunctivitis. Unfortunately, antibiotics are ineffective at treating viral conjunctivitis and have no therapeutic impact and the patient will remain contagious and can spread the disease to others. Precribing unnecessary antibiotics can also delay proper treatment, and can lead to potential allergies, toxicity, or even antibiotic resistance.
EKC symptoms include inflammation in the conjunctiva (conjunctivitis) and in the cornea (keratitis), severe pain, oedema, diminished eyesight, tearing, sensitivity to light, feeling or sensation that a foreign body is present in the eye, and the development of pseudo-membranes. During the acute phase, which persists for approximately two-three weeks, viruses are present and replicating. In the typical case, first one eye is infected, after which the infection spreads to the other eye within two to three days. Both eyes are affected in 60% of cases. The infection in the first eye is typically the more serious. In approximately 20 – 50% of patients, corneal opacities are developed that result in deteriorating vision that remains for weeks and months, and in rare cases even years.
EKC is a serious and contagious eye infection (conjunctiva and cornea) caused by mainly adenoviruses type: 8, 19, 37. Recently also Ad53, Ad54 and Ad 56 have been identified as a cause of EKC, and these viruses are closely related to Ad 8, Ad19, and Ad37. More than 50 serotypes of adenovirus have been isolated, and at least 19 documented serotypes cause eye infection. The most commonly associated serotypes that cause EKC include adenovirus 8, 19, and 37, and less frequently and in less severe forms, serotypes 2-5, 7, 9, 10, 11, 14, 16, 21, and 29, where Ad 3 and 4 are more common. Because of low levels of natural immunity against adenovirus in the general population, e.g. adenovirus type 8 antibodies are found in <5% of the general population in the US, every individual is considered susceptible to infection.
Since the disease is often epidemic in nature, it is called epidemic keratoconjunctivitis. Adenovirus conjunctivitis is a reportable infection in Germany and is classified as a Category IV infectious disease by Japan’s National Epidemiological Surveillance of Infectious Diseases (NESID) with mandated collection, analysis and publication of reports on occurrences.
Adenovirus is spread mainly via respiratory droplets or by direct contact with the eyes by fingers or other objects. The incubation period is 2-14 days, and a person may remain infectious for 10-14 days after symptoms develop. EKC is transferred between individuals via physical contact, e.g. from eye to hand, from hand to a doorknob, from a doorknob to another person’s hand, and then to an uninfected eye. Viruses causing EKC can survive, e.g. on doorknobs, towels, etc., for months. Adequate infection control measures must be followed in order to prevent and reduce epidemic outbreaks. Either as a result of their symptoms, or on the recommendation of a physician in light of the highly contagious nature of the disease, patients are unable to attend work or school. Approximately 45% of people in a patient’s close surroundings, e.g., family members, will become infected. Although EKC normally clears up within 2-3 weeks, the costs to society both in terms of healthcare costs, and the loss of production, because of its highly contagious nature, are substantial. The disease may also have long-term implications for eyesight and recurrence.
Current clinical practice and recommendations
Currently, no clinically applicable specific anti-viral therapy is available either to shorten the course of the infection, to improve the distressful clinical symptoms, to stop viral replication, or to prevent the development of corneal opacities.
Antibiotics are ineffective at treating viral conjunctivitis and have no therapeutic impact on virus and the patient will remain contagious and can spread the disease to others. Prescribing unnecessary antibiotics can also delay proper treatment, and can lead to potential allergies, toxicity, or even antibiotic resistance. A publication concluded that general physians prescribe topical antibiotics in more than 90% of the cases, despite understanding that more than half of the cases are of viral origin and only a third could discriminate between bacterial and viral, and even bacterial infection are self-limiting. Treatment of the acute phase of the infection with topical steroids has been widely used. However, recent findings conclude that steroids may prolong the persistence of infection in the cornea, and frequent use may lead to long-lasting dry eye symptoms. The use of steroids should therefore be avoided in both the acute and the chronic phases of the disease.
Large unmet medical need
External ocular infections caused by adenoviruses are among the most common eye infections seen worldwide and conjunctivitis represents a large proportion of visits to ophthalmologists. A report states that ocular adenoviral infection represents a significant public health problem in the US and worldwide. Although exact numbers are difficult to determine, estimates suggest the number of cases of ocular adenoviral infections may be as high as 15-20 million per year in the US. Due to the nature of the disease, the exact number of incidences of EKC is not known and it is assumed that the majority of cases are not recorded. EKC is particularly problematic in Japan where there are more than one million cases of EKC each year, as reported in several sources.
EKC is a disease where there is a lack of effective treatment and a large unmet medical need. A pharmaceutical that could be used for the treatment of EKC and for the prevention of its spread, would be highly desirable for patients suffering from the disease, for those who come into contact with such patients, and for treating physicians.
Large medical need for treatment for EKC
Survey among European ophthalmologists highlights that there is a large unmet medical need for treatment of EKC. The majority of physians state that there is a high or very high medical need for an effective treatment.